Abstract
Information on the clinical traits associated with bronchial neutrophilia in asthma is scant, preventing its recognition and adequate treatment. We aimed to assess the clinical, functional and biological features of neutrophilic asthma and identify possible predictors of bronchial neutrophilia.
The inflammatory phenotype of 70 mild-to-severe asthma patients was studied cross-sectionally based on the eosinophilic/neutrophilic counts in their bronchial lamina propria. Patients were classified as neutrophilic or non-neutrophilic. Neutrophilic asthma patients (neutrophil count cut-off: 47.17 neutrophils·mm−2; range: 47.17–198.11 neutrophils·mm−2; median: 94.34 neutrophils·mm−2) were further classified as high (≥94.34 neutrophils·mm−2) or intermediate (47.17– <94.34 neutrophils·mm−2). The effect of smoking ≥10 pack-years was also assessed.
Neutrophilic asthma patients (n=38; 36 mixed eosinophilic/neutrophilic) had greater disease severity, functional residual capacity, inhaled corticosteroid (ICS) dose and exacerbations, and lower forced vital capacity (FVC) % pred and forced expiratory volume in 1 s (FEV1) reversibility than non-neutrophilic asthma patients (n=32; 28 eosinophilic and four paucigranulocytic). Neutrophilic asthma patients had similar eosinophil counts, increased bronchial CD8+, interleukin (IL)-17-F+ and IL-22+ cells, and decreased mast cells compared with non-neutrophilic asthma patients. FEV1 and FVC reversibility were independent predictors of bronchial neutrophilia in our cohort. High neutrophilic patients (n=21) had increased serum IgE levels, sensitivity to perennial allergens, exacerbation rate, oral corticosteroid dependence, and CD4+ and IL-17F+ cells in their bronchial mucosa. Excluding smokers revealed increased IL-17A+ and IL-22+ cells in highly neutrophilic patients.
We provide new evidence linking the presence of high bronchial neutrophilia in asthma to an adaptive immune response associated with allergy (IgE) and IL-17/22 cytokine expression. High bronchial neutrophilia may discriminate a new endotype of asthma. Further research is warranted on the relationship between bronchoreversibility and bronchial neutrophilia.
Abstract
Asthma with high bronchial neutrophilia is associated with increased serum IgE, perennial allergy and IL-17 expression combined with CD4+ cells. This new endotype is clinically associated with exacerbation rate in the previous year and OCS dependence. http://bit.ly/2ZqboJ2
Footnotes
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Support statement: This study was supported by Ricerca Sanitaria Finalizzata Regione Piemonte (2472/2007 and 38097/2008). Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: V. Carriero has nothing to disclose.
Conflict of interest: F. Bertolini has nothing to disclose.
Conflict of interest: A. Folino has nothing to disclose.
Conflict of interest: A. Mannelli has nothing to disclose.
Conflict of interest: A. Di Stefano has nothing to disclose.
Conflict of interest: I. Gnemmi has nothing to disclose.
Conflict of interest: R. Torchio has nothing to disclose.
Conflict of interest: F.L.M. Ricciardolo has nothing to disclose.
Conflict of interest: M. Bullone has nothing to disclose.
- Received January 10, 2019.
- Accepted July 29, 2019.
- Copyright ©ERS 2019